ライフサイエンスコーパス: GMF

1 GMF debranches filaments by a mechanism related to cofil

2 GMF does not bind monomeric ATP- or ADP-actin, confirmin

3 GMF induced two distinct open conformations of Arp2/3 co

4 GMF is implicated in both Arp2/3 debranching and inhibit

5 GMF promotes the differentiation of mammalian glia and n

6 GMF+/+ (Wt) mice developed severe EAE with a maximal mea

7 GMF-deficient mice showed reduced glial activation and s

8 GMF-null mice developed normally without gross abnormali

9 8, P < 0.001; T(1) r = -0.59, P = 0.002) and GMF (T(2) r = -0.73, P < 0.001; T(1) r = -0.53, P = 0.00

10 Therefore, ADF/cofilin and GMF, members of the same superfamily, appear to have evo

11 y effects on Arp2/3 complex with Coronin and GMF.

12 nstrate the critical role of GMF in EAE, and GMF antibody as a potent anti-inflammatory therapeutic a

13 system (CNS) of GMF+/+ (wild type) mice and GMF-/- (GMF-knockout) mice at the peak of EAE induced by

14 lization of GMF with four injections of anti-GMF antibody 5 to 11 days post immunization delayed the

15 3 networks are remodeled by proteins such as GMF, which blocks the actin-Arp2/3 interaction [4, 5], a

16 growth factor, glia maturation factor-beta (GMF).

17 e mice revealed profound differences between GMF-antibody treated mice and isotype matched control-an

18 examined the potential relationship between GMF or lack of it with learning and memory using the T-m

19 ltiple sclerosis with control subjects, BPF, GMF and WMF were significantly reduced (P < 0.001 for al

20 n-promoting factor N-WASP is not affected by GMF, whereas nucleation activated by the WCA region of W

21 on the regulation of MAP kinase cascades by GMF.

22 es activation of the death domain caspase by GMF overexpression.

23 -defective adenovirus construct of GMF cDNA (GMF-V) induced overexpression of GMF protein in neurobla

24 In cultured S2R(+) cells, GMF silencing resulted in an increase in the width of la

25 We found that S. cerevisiae GMF (also called Aim7) localizes in vivo to cortical act

26 obtained from the GMF-transfected cells (CM-GMF) and tested on primary neuronal cultures, consisting

27 ntribute to the neuroprotective effect of CM-GMF.

28 or, eliminated the neurotrophic effect of CM-GMF; whereas anti-NGF antibody was ineffective in preven

29 ted the RT-PCR results and indicated that CM-GMF contained greater concentrations of BDNF and NGF pro

30 We demonstrated that the CM-GMF had an enhanced neurotrophic effect as well as an in

31 In conclusion, GMF upregulates the expression of BDNF and NGF in C6 cel

32 sed Abeta1-42 in the brain of GMF-deficient (GMF-KO) mice, recently prepared in our laboratory.

33 nd a likely photoreceptor of the directional GMF response.

34 emonstrate that neutralization of endogenous GMF with an affinity purified GMF antibody significantly

35 several protein kinases, and that endogenous GMF is rapidly phosphorylated upon stimulation of astroc

36 etween actin-WCA and glia maturation factor (GMF) for binding to Arp2/3 complex suggests that during

37 t over-expression of glia maturation factor (GMF) in glial cells cause excessive production and secre

38 Glia maturation factor (GMF) is a member of the actin-depolymerizing factor (ADF

39 Glia maturation factor (GMF) is a unique brain protein localized in astrocytes a

40 at the brain protein glia maturation factor (GMF) is involved in intracellular signaling in glia.

41 ly demonstrated that glia maturation factor (GMF), a 17-kDa brain protein, can be phosphorylated in t

42 ort that recombinant glia maturation factor (GMF), a 17-kDa brain protein, inhibits the activity of m

43 rved previously that glia maturation factor (GMF), a 17-kDa brain protein, is rapidly phosphorylated

44 Glia maturation factor (GMF), a protein primarily localized in the central nervo

45 inhibitory ligands: glia maturation factor (GMF), Coronin, and Arpin.

46 Glia maturation factor (GMF), discovered and characterized in our laboratory, is

47 We show that glia-maturation factor (GMF), which is an Arp2/3 complex inhibitor and actin fil

48 the yeast homolog of glia maturation factor (GMF), which is structurally related to the actin filamen

49 olog of ADF/cofilin, glia maturation factor (GMF).

50 eraction with ADF/cofilin support a role for GMF in promoting the remodeling and/or disassembly of br

51 ted with the two suggested binding sites for GMF.

52 ter fraction (WMF) and grey matter fraction (GMF).

53 Further, GMF inhibits nucleation of new daughter filaments.

54 Furthermore, GMF phosphorylated by protein kinase C (PKC), but not by

55 Furthermore, GMF synergized with Coronin in inhibiting actin nucleati

56 (CNS) of GMF+/+ (wild type) mice and GMF-/- (GMF-knockout) mice at the peak of EAE induced by immuniz

57 egion of WAVE2 is slightly inhibited at high GMF concentrations.

58 However, GMF lacks detectable actin binding or severing activity

59 8 carry out opposing functions and implicate GMF as a regulator of major cellular events.

60 The structural abnormality in GMF-null mice explained their impaired ability for both

61 Change in GMF correlated only modestly with the change in T2 lesio

62 This activity and mechanism are conserved in GMF homologs from evolutionarily distant species.

63 flammation and demyelination was detected in GMF-antibody-treated mice at days 8, 16, and 24 post imm

64 sed incidence and reduced severity of EAE in GMF-antibody-treated mice was consistent with the signif

65 s show that memory retention was improved in GMF-KO mice compared to Wt controls following Abeta infu

66 s undergoing guided migration was reduced in GMF mutant flies.

67 The phosphomimetic mutation S2E in GMF inhibits this interaction.

68 nd F-actin binding site on cofilin, which in GMF appears to contact the first actin subunit in the da

69 e growth factor from PC12 leads to increased GMF phosphorylation with a time course similar to that r

70 Depletion of GMF gene by introducing GMF-specific siRNA (GsiRNA) completely blocked both acti

71 Brugia malayi GMF (BmGMF) is also related to a large family of eukaryo

72 ty and mechanism are conserved for mammalian GMF.

73 thermal titration calorimetry that mammalian GMF has very low affinity for ATP-bound Arp2/3 complex b

74 d whether this activity extends to mammalian GMF have remained open questions.

75 This study investigated whether or not GMF plays a role in the survival-promoting and neuroprot

76 border cells is diminished in the absence of GMF.

77 hing, suggesting that the higher affinity of GMF for ADP-Arp2/3 complex plays a physiological role by

78 It appears that the mutual augmentation of GMF and PKA, and the stimulating effect of PKC, both ser

79 of AD, we infused Abeta1-42 in the brain of GMF-deficient (GMF-KO) mice, recently prepared in our la

80 lammatory cytokines/chemokines in the CNS of GMF-KO mice and increased expression in Wt mice with EAE

81 ators in the central nervous system (CNS) of GMF+/+ (wild type) mice and GMF-/- (GMF-knockout) mice a

82 3-dependent site of Tau was a consequence of GMF-overexpression in N18 cells.

83 eplication-defective adenovirus construct of GMF cDNA (GMF-V) induced overexpression of GMF protein i

84 ese Abeta1-42 effects in primary cultures of GMF-KO astrocyte and microglia were reversed by reconsti

85 Depletion of GMF gene by introducing GMF-specific siRNA (GsiRNA) comp

86 er deals with the behavior of mice devoid of GMF protein (knockout).

87 orward in deciphering the in vivo effects of GMF and supports the interaction of underlying mechanism

88 were reversed by reconstituted expression of GMF.

89 se (RSK) enhances the inhibitory function of GMF on ERK; protein kinase C (PKC) and casein kinase II

90 Immunoprecipitation of GMF from cell extracts using its specific antibody copre

91 wo factors play a role in the interaction of GMF with Arp2/3 complex.

92 he generation of various phospho-isoforms of GMF may explain its modulation of signal transduction at

93 ivation and large increases in the levels of GMF as well as induction of inflammatory cytokine/chemok

94 Neutralization of GMF with four injections of anti-GMF antibody 5 to 11 da

95 ee of fifteen Wt mice as compared to none of GMF-KO mice died of EAE.

96 Overexpression of GMF also increased caspase-3 activity, an early marker o

97 f GMF cDNA (GMF-V) induced overexpression of GMF protein in neuroblastoma (N18) cells caused cytotoxi

98 Studies with overexpression of GMF using adenovirus vector have uncovered its regulator

99 A preliminary phosphorylation of GMF by protein kinase A (PKA) dramatically increases its

100 d p38 is supported by the phosphorylation of GMF upon cellular stimulation by forskolin (blocked by P

101 ese results demonstrate the critical role of GMF in EAE, and GMF antibody as a potent anti-inflammato

102 r results indicate a novel mediatory role of GMF in the neuro-inflammatory pathway of Abeta and its p

103 containing putative phosphorylation sites of GMF, we demonstrate that PKA is capable of phosphorylati

104 Non-phosphorylated GMF or GMF phosphorylated by other kinases exhibits only minima

105 The transfected cells overexpressed GMF intracellularly, but did not secrete the protein.

106 e other three enzymes that can phosphorylate GMF, only p90 ribosomal S6 kinase (RSK) enhances the inh

107 Non-phosphorylated GMF or GMF phosphorylated by other kinases exhibits only

108 d that protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor (IC50 = 3 nM) of the ERK1/ERK2

109 d that protein kinase A (PKA)-phosphorylated GMF is a potent inhibitor of extracellular signal-regula

110 we present evidence that PKA-phosphorylated GMF also promotes (11-fold) the catalytic activity of PK

111 The inhibitory effect of PKA-phosphorylated GMF is specific, as it does not suppress the activity of

112 report that, by contrast, PKA-phosphorylated GMF strongly enhances the activity of a related but dist

113 The inhibition of ERK by PKA-phosphorylated GMF suggests that GMF could be one of the mediators of t

114 On the other hand, that RSK-phosphorylated GMF also inhibits ERK implies a negative feedback loop i

115 The intracellular interaction of PKA, GMF, and p38 is supported by the phosphorylation of GMF

116 GSK-3beta, and lithium completely prevented GMF-dependent activation of caspase-3.

117 of endogenous GMF with an affinity purified GMF antibody significantly decreased the inflammation, s

118 cells from Wt mice transferred to recipient GMF-KO mice caused very mild and with low incidence of E

119 n-activated protein (MAP) kinase, suggesting GMF as a bifunctional regulator of the MAP kinase cascad

120 rthermore, genetic studies demonstrated that GMF cooperates with the Drosophila homolog of Aip1 (flar

121 Previously we demonstrated that GMF is required in the induced production of proinflamma

122 We previously demonstrated that GMF mediates the experimental autoimmune encephalomyelit

123 escent wave microscopy, we demonstrated that GMF potently stimulates debranching of actin filaments p

124 To test the hypothesis that GMF is involved in the pathogenesis of AD, we infused Ab

125 Taken together our results imply that GMF is involved in the signaling leading to the activati

126 We further show that GMF binds to the Arp2/3 complex with low nanomolar affin

127 ection fluorescence microscopy, we show that GMF depends on two separate surfaces for debranching.

128 Together, these data suggest that GMF binds Arp2/3 complex to both "prune" daughter filame

129 Together, the results suggest that GMF functions by a mechanism similar to that of other AD

130 These data suggest that GMF functions in vivo to promote the disassembly of Arp2

131 Our data suggest that GMF play a critical role in CNS inflammation.

132 ERK by PKA-phosphorylated GMF suggests that GMF could be one of the mediators of the suppressive eff

133 RT-PCR verified that GMF-transfected C6 cells had increased mRNA levels for B

134 onditioned medium (CM) was obtained from the GMF-transfected cells (CM-GMF) and tested on primary neu

135 The decrease in glial activation in the GMF-KO mice is also associated with significant reductio

136 tional response to periodic rotations of the GMF vector in two insect species.

137 Modulation of GMFbeta, a ubiquitous GMF isoform, by depletion or overexpression resulted in

138 n decrease in grey matter fractional volume (GMF, as a fraction of total intracranial volume) was -0.

139 However, with beam walking, GMF-knockout mice performed poorly and failed to learn.

140 disassembly of aged actin filaments, whereas GMF interacts specifically with Arp2/3 complex at branch

141 6+/-0.5 by day 16 post-immunization, whereas GMF-KO mice showed significantly delayed EAE with an ave

142 protective effects, we investigated whether GMF-transfection upregulated the expression of neurotrop

143 d to cofilin-mediated severing, but in which GMF has evolved to target molecular junctions between ac

144 n of GSK-3beta occurred after infection with GMF-V when compared with mock and lacZ controls.

145 nd by the co-immunoprecipitation of p38 with GMF from cell lysates.

146 glioma cells were transfected in vitro with GMF utilizing an adenovirus vector.